MLT GlobeHematology: Hemolytic anemias & hemoglobinopathies – page 6
120 Hematology MCQs on Hemolytic anemias & hemoglobinopathies with answers and explanations.
A man from Malaysia has mild or no anemia. His smear shows rigid oval cells, many with one or two transverse slits. The underlying defect is most likely:
Southeast Asian ovalocytosis results from a band 3 deletion producing rigid stomatocytic ovalocytes, often with little hemolysis and some protection against malaria. Alpha-spectrin mutations cause ordinary elliptocytosis with thin, non-slit elliptocytes.
FLAER, a reagent used in flow cytometric testing for PNH on white cells, binds directly to:
FLAER is a fluorescent inactive aerolysin that binds the GPI anchor, so GPI-deficient granulocytes and monocytes show no staining. Anti-CD59 antibodies, not FLAER, are used to detect GPI-deficient red cells.
A cold autoantibody causing hemolysis in a patient with infectious mononucleosis most often has which specificity?
EBV infection is associated with transient cold agglutinins of anti-i specificity, which react best with cord cells. Anti-I is the typical specificity after Mycoplasma infection.
A Pakistani patient has a band in the HbS position on alkaline electrophoresis, but a negative solubility test. On acid (citrate agar, pH 6.0–6.2) electrophoresis the band moves with HbA. The most likely variant is:
HbD and HbG move with HbS at alkaline pH but with HbA at acid pH, and they do not sickle. HbS keeps a separate position on acid agar and gives a positive solubility test.
On cation-exchange HPLC, a patient shows 28% hemoglobin eluting in the HbA2 window, with mild microcytosis. The most likely explanation is:
HbE co-elutes with HbA2 on most HPLC systems; values around 25–30% indicate HbE trait. In beta-thalassemia trait HbA2 is only mildly raised, usually 3.5–7%.
Using an acid-elution (Kleihauer) stain or anti-HbF flow cytometry, HbF is spread evenly in all red cells of a healthy adult with HbF 25%. This pattern suggests:
Deletional HPFH shows a pancellular HbF distribution, while delta-beta thalassemia and hydroxyurea therapy give a heterocellular pattern. Fetomaternal hemorrhage shows a small separate population of strongly stained cells.
A man has an isolated raised hemoglobin, normal white cells and platelets, and a family history of the same. The oxygen P50 is low. The most likely cause is:
High-affinity variants hold oxygen tightly (low P50), causing tissue hypoxia and a compensatory rise in erythropoietin and red cells. HbM variants cause cyanosis from methemoglobin, not erythrocytosis with low P50.
A patient with Clostridium perfringens sepsis develops sudden, massive intravascular hemolysis with many spherocytes. The main mechanism is:
The C. perfringens alpha-toxin is a phospholipase (lecithinase) that digests membrane lipids, forming spherocytes and causing rapid lysis. The DAT is negative, so an IgG autoantibody is not the cause.
A couple both have alpha-thalassemia trait with two alpha genes deleted. Their fetus is at risk of Hb Bart's hydrops fetalis only if:
Only the cis (--/αα) arrangement can pass a chromosome with no alpha genes; two such chromosomes give --/--. Parents with the trans (-α/-α) arrangement can only pass -α, so the worst outcome is -α/-α.
Hb Constant Spring, common in Southeast Asia, is an alpha-chain variant caused by:
A mutation in the alpha2 termination codon adds 31 amino acids, producing an unstable chain made in small amounts, so it behaves like an alpha-thalassemia allele. Delta-beta fusion describes Hb Lepore.
Hb Lepore is formed by:
Unequal crossing over joins the start of the delta gene to the end of the beta gene. The delta-beta hybrid chain is made poorly, giving a beta-thalassemia phenotype. Beta-26 glutamic acid to lysine is HbE.
A young adult with painful crises has MCV 66 fL, normal ferritin and HPLC showing HbS 72%, HbA 16%, HbA2 5.5% and HbF 6.5%. The most likely diagnosis is:
HbS greater than HbA, microcytosis and raised HbA2 indicate one beta-S gene with a beta+ thalassemia gene that makes a little HbA. In sickle cell trait HbA exceeds HbS and indices are normal; HbSS has no HbA.
On alkaline (pH 8.4–8.6) hemoglobin electrophoresis, which hemoglobin moves farthest toward the anode?
HbH (β4) and Hb Bart's (γ4) carry a stronger negative charge and run ahead of HbA. HbS and HbC are more positive and move more slowly, with HbC closest to the origin.
A woman with microcytosis has ferritin 5 µg/L (5 ng/mL) and HbA2 3.0% on HPLC. Several relatives have beta-thalassemia trait. The best interpretation is:
Severe iron deficiency reduces HbA2 synthesis and can mask beta-thalassemia trait, so HbA2 should be rechecked once iron is replaced. A normal value in an iron-deficient patient does not exclude the trait.
A woman heterozygous for a G6PD-deficient allele has a normal G6PD screening test. The best explanation is:
Random X-inactivation (lyonization) makes heterozygous women mosaics; the normal cell population can give a normal screen, so quantitative or cytochemical testing may be needed. The G6PD gene is on the X chromosome.
A child given ceftriaxone develops sudden severe intravascular hemolysis with hemoglobinuria. The DAT is positive with anti-C3. The mechanism is best described as:
Ceftriaxone-dependent antibodies bind only when the drug is present, activating complement and causing brisk intravascular lysis with C3 on the cells. Hapten-type (penicillin) reactions are IgG-mediated and extravascular.
Chronic primary cold agglutinin disease in an older adult is most often associated with:
Primary cold agglutinin disease is now seen as a low-grade clonal B-cell disorder, usually producing IgM kappa anti-I. Mycoplasma causes a transient, secondary polyclonal cold agglutinin, and IgG anti-P is the Donath–Landsteiner antibody.
A patient with PNH on a C5 inhibitor (eculizumab) still has mild anemia, a raised reticulocyte count and a new positive DAT with anti-C3 only. The best explanation is:
Blocking C5 prevents membrane attack complex lysis, but C3 still deposits on CD55-deficient cells, and these are cleared by macrophages. This extravascular hemolysis gives a C3-only positive DAT.
In intravascular hemolysis, once haptoglobin is saturated, free heme released from hemoglobin is carried mainly by:
Hemopexin binds free heme and carries it to the liver, so it falls in severe intravascular hemolysis. Transferrin carries free ferric iron, not heme, and ferritin is a storage protein.
A 17-year-old has DAT-negative hemolytic anemia, raised liver enzymes and a new tremor. Which test is most useful next?
Wilson disease can present with acute hemolysis when copper is released from the liver, along with liver and neurological signs. Low ceruloplasmin supports the diagnosis; lead causes stippling and anemia but not this combination.